Soranefib safe, effective in hepatocellular carcinoma

Compared with placebo, sorafenib improved time to progression and overall survival in patients in the Asia-Pacific region with hepatocellular carcinoma.

“If we put the results of the SHARP and Asia-Pacific studies together, the benefit of sorafenib in terms of overall survival, time to progression and progression-free survival were similar, although the Asia-Pacific study included a group of patients with more advanced stage disease,” said Ann-Lii Cheng, MD, PhD, department of internal medicine at the National Taiwan University Hospital in Taiwan, during his presentation at the 2008 ASCO Annual Meeting.

Cheng and colleagues conducted a phase-3 trial to determine the safety and efficacy of soranefib (Nexavar, Bayer) in patients with hepatocellular carcinoma living in the Asia-Pacific region. The study included 226 patients who were randomly assigned to soranefib 400 mg twice per day (n=150) or placebo (n=76).

“Our key finding was that median overall survival improved from 4.2 months to 6.5 months, yielding an improvement of 47%. The hazard ratio was 0.68 and the P value was highly significant at 0.014,” Cheng said.

Median time to progression improved from 1.4 months in the placebo arm to 2.8 months in the sorafenib arm (HR=0.57; P<.001). The researchers did not observe a significant difference in time to symptomatic progression.

“We can conclude from the AP Liver Cancer Study that sorafenib significantly improved overall survival over placebo in advanced liver cancer. Sorafenib was well tolerated and had manageable side effects; it is effective in patients with HCC from the Asia-Pacific region.” – by Stacey L. Adams

From analyzing these data and the SHARP trial data, there are differences in the geographical population, and it seems clear that in the Asian trial there are differences in terms of the disease being more advanced.

The results of the Asian trial are consistent with those reported by the SHARP investigators. Outcome benefits are achieved without relevant objective responses, the poor outcomes observed in both arms of the Asian trial reflect the inclusion of a high proportion of patients with adverse prognostic factors and the high rate of hand-foot skin reaction in the Asian trial patients deserve further investigation.

Regarding who we should treat, sorafenib is indicated in patients with advanced hepatocellular carcinoma, meaning symptomatic or with vascular invasion or metastases, and in those patients progressing after local regional therapies regardless of ethnicity. The next steps in trial design and research should target other unmet medical needs such as adjuvant therapies after local regional therapies, resection or a combination of molecular therapies.

– Josep Llovet, MD

Director, HCC Research Program, Mt. Sinai School of Medicine, New York

For more information:
Cheng AL, Kang Y, Chen Z et al. Randomized phase III trial of sorafenib versus placebo in Asian patients with advanced hepatocellular carcinoma. Presented at: 2008 ASCO Annual Meeting; May 30-June 3, 2008; Chicago.